Excipient powders frequently exhibit poor flow and compaction behavior. Various techniques such as wet granulation, spray drying, mechanofusion, and grinding have been employed to improve the flow and compaction behavior.
Cellulose derivatives are important polysaccharide derivatives. These are widely used in various industrial applications, for example, in personal care, pharmaceutical, agricultural construction and energy. One of the important applications of the cellulose polymers, particularly water-soluble cellulose derivatives, is their incorporation as excipients in sustained release dosage forms. Sustained release dosage forms are designed to release a drug at a predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects. This can be achieved through a variety of formulations, including polymer matrix in dosage forms. Sustained release pharmaceutical dosage forms maintain therapeutic serum levels of medicaments and minimize the effects of missed doses of drugs caused due to lack of patient compliance.
U.S. Pat. No. 4,734,285 assigned to Dow Chemical Company discloses delayed release solid tablets of a therapeutically active composition and a process to prepare such a composition. Fine particles, which can pass a 100 mesh screen (149 micrometer mesh size) and preferably 140 mesh screen (105 micrometer mesh size), of hydroxypropyl methylcellulose ether composition are present as an excipient in the solid tablet. These fine particles are very small in size and show poor flow properties. Poor particle flow can lead to consolidation of the powder bed in processing equipment, such as storage bins and tablet press feed hoppers. Problems can include increased inconsistency in tablet weight or tablet crushing strength from tablet-to-tablet as well as inconsistency in the amount of active ingredient incorporated into each dosage form.
WO2004/022601 assigned to JRS Pharma LP and U.S. Pat. No. 5,585,115 assigned to Edward H. Mendell Co., Inc. disclose an agglomerated microcrystalline cellulose blend containing silicon dioxide, purported to have improved compressibility. The disclosure states that silicon dioxide is a critical component to improve compressibility. The two step process described includes spray granulation followed by wet granulation. The prepared granules in this process are further dried using heat, which is not advantageous. However, granulation is time consuming and adds cost to the process due to the time lost, additional labor, energy consumption and additional equipment required.
Several processes for drying-grinding moist cellulose derivatives are known in the art, such as described in the patent applications GB 2262527A; EP 0 824 107 A2; EP-B 0 370 447 (equivalent to U.S. Pat. No. 4,979,681); EP 1 127 895 A1 (equivalent to U.S. Pat. No. 6,509,461); EP 0 954 536 A1 (equivalent to U.S. Pat. No. 6,320,043); WO96/00748 A1; WO2011/046679 (equivalent to US 2012/187225) and WO2012/138532.
US2012/160944A1 assigned to ICEUTICA PTY LTD discloses a method to produce nano and micro-particle powders of a biologically active material which have improved powder handling properties using dry milling process.
WO2012/116402A1 assigned to University of Monash discloses binder powders for use in powder material processing and processes for their preparation by using techniques such as spray drying and mechanofusion. These processes lead to reduction in particle size of the polymer. Moreover, these processes are costly and time consuming.
The increase in flow of cellulose polymers by co-milling microcrystalline cellulose with nano-silica is described in J. Pharm. Sci. 2011 November; 100(11):4943-52, Chattoraj S, Shi L, Sun CC.
Moreover, spray drying, mechanofusion, magnetic assisted impaction, hybridizer and grinding require specialized instruments that are commonly not available at manufacturing units.
Surprisingly, it has been found that bulk density and flowability of cellulose derived polymer can be increased by a novel continuous process comprising coprocessing the polymer and a coprocessing agent using high shear.
Thus, the present invention relates to a coprocessed excipient composition comprising cellulose derived polymer and a deagglomerated coprocessing agent. The coprocessed excipient is prepared in a continuous process and has excellent compactability and improved flow property as measured by Johanson flow rate number increased from 1.1 to 5.0 fold, is characterized by a Brookfield cohesion less than 0.20 kPa, a bulk density of at least 0.249 g/ml. The coprocessing agent is fumed silica, colloidal silica, silicon dioxide or a combination thereof.